SPECT/CT Fusion in the Diagnosis of Hyperparathyroidism.

OBJECTIVES
In this study, we aimed to analyze the relationship between the diagnostic ability of fused single photon emission computed tomography/ computed tomography (SPECT/CT) images in localization of parathyroid lesions and the size of adenomas or hyperplastic glands.


METHODS
Five patients with primary hyperparathyroidism (PHPT) and 4 patients with secondary hyperparathyroidism (SHPT) were imaged 15 and 120 minutes after the intravenous injection of technetium99m-methoxyisobutylisonitrile ((99m)Tc-MIBI). All patients underwent surgery and 5 parathyroid adenomas and 10 hyperplastic glands were detected. Pathologic findings were correlated with imaging results.


RESULTS
The SPECT/CT fusion images were able to detect all parathyroid adenomas even with the greatest axial diameter of 0.6 cm. Planar scintigraphy and SPECT imaging could not detect parathyroid adenomas with an axial diameter of 1.0 to 1.2 cm. Four out of 10 (40%) hyperplastic parathyroid glands were diagnosed, using planar and SPECT imaging and 5 out of 10 (50%) hyperplastic parathyroid glands were localized, using SPECT/CT fusion images.


CONCLUSION
SPECT/CT fusion imaging is a more useful tool for localization of parathyroid lesions, particularly parathyroid adenomas, in comparison with planar and or SPECT imaging.


Introduction
Technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) parathyroid scintigraphy is a useful tool for localization of lesions in hyperparathyroidism (HPT). However, few reports have reviewed the diagnostic ability of single photon emission computed tomography/ computed tomography (SPECT/CT) imaging in HPT using fusion images. In the present study, we aimed to evaluate the correlation between the diagnostic ability of fused SPECT/CT images in localization of parathyroid lesions and the size of adenomas or hyperplastic glands.

Methods
Nine patients with HPT underwent MIBI using SPECT/CT imaging between May 2012 and April 2014. Five patients were diagnosed with primary hyperparathyroidism (PHPT) and 4 patients diagnosed with secondary hyperparathyroidism (SHPT) with chronic renal failure. All patients underwent surgery. Five lesions were identified as parathyroid adenomas, while 10 lesions were identified to be parathyroid hyperplasia.
Parathyroid hormone and calcium levels remained within the normal range in 8 patients after the surgery, although parathyroid hormone level increased after the surgery in 1 patient with PHPT.
The SPECT/CT equipment used in this study was Symbia T16 (Siemens, USA), which combines 16-slice multidetector CT and SPECT. Six-hundred MBq of 99m Tc-MIBI was injected intravenously in all patients. Early and delayed neck and upper thorax planar images were acquired 15 and 120 minutes after the injection, respectively. SPECT/ CT acquisition was performed immediately after obtaining the delayed planar images; SPECT images were obtained using the SPECT/CT system. Overall, 90 projections (128×128 matrix) were acquired (20 seconds each), with a total duration of 15 minutes for the whole SPECT/CT procedure.
CT was performed immediately after SPECT imaging. The main CT parameters were 130 kV, 25 mAs, and a 1.2 mm slice thickness; no intravenous contrast medium was used. SPECT/CT data were analyzed on a Syngo workstation, which provided transaxial, coronal, and sagittal slices of SPECT, CT, and fused SPECT-CT data. The size of the lesions was obtained from the pathology reports.

Statistical analysis
To compare the mean size of lesions in two groups, we used two-tailed student's t-test. For statistical analysis, Excel 2012 was used (SSRI Co., Ltd., Japan). P-value less than 0.05 was considered statistically significant.

Results
Five parathyroid adenomas and five hyperplastic glands were correctly localized, using the SPECT/CT fusion images. In contrast, 5 hyperplastic parathyroid glands could not be detected by fusion images.
Three out of five parathyroid adenomas were localized on 99m Tc-MIBI planar scintigraphy and SPECT images, whereas 5 parathyroid adenomas were localized on the SPECT/CT fusion images. All parathyroid adenomas with the largest axial diameter of 0.6 cm or more were localized on the SPECT/CT fusion images. In contrast, parathyroid adenomas with the greatest axial diameter of 1.0 to 1.2 cm were not localized on planar 99m Tc-MIBI scintigraphy or SPECT images ( Figure 1). The mean size of the detected and undetected parathyroid adenomas in planar scintigraphy was 1.3±0.6 and 1.1±0.1 cm, respectively (P=0.7). The corresponding values were 1.3±0.6 and 1.1±0.1 cm in SPECT imaging, respectively (P =0.7). The mean size of detected adenomas was 1.2±0.4 cm, based on the SPECT/CT images, and no adenoma remained undetected, using SPECT/CT images.
Four out of 10 (40%) hyperplastic parathyroid glands were localized, using planar 99m Tc-MIBI scintigraphy and SPECT images, while 5 out of 10 (50%) hyperplastic parathyroid glands were localized, using the SPECT/CT fusion images. Five hyperplastic parathyroid glands with the greatest axial diameter of > 0.4 cm were correctly localized, using the SPECT/CT fusion images.
The mean size of 5 hyperplastic parathyroid glands detected on SPECT/CT fusion images was 0.6±0.2 cm (range 0.4∼0.9cm). Five scintigraphically undetected hyperplastic parathyroid glands had the mean greatest axial diameter of 0.6±0.3 cm (range: 0.4-1.1 cm); there was not a statistically significant difference between the two groups (P=1.0). Although this negative result may reflect the small sample size in our study, it seems that other factors may play a role in the detection of hyperplastic glands, using scintigraphy (Table 1). Figure 1 shows a patient with PHPT due to left inferior parathyroid adenoma, which is not localized by planar scintigraphy, while detected by SPECT/CT imaging. Figure 2 shows a patient with SHPT due to right inferior hyperplastic parathyroid gland, which is not localized using planar scintigraphy, while detected by SPECT/CT imaging.

Discussion
The main advantage of SPECT/CT systems is their application for the acquisition of highprecision fusion images, using both CT and SPECT imaging. Fusion images can be used for making a differential diagnosis between benign and malignant diseases in different body organs, determining the stage of the lesion, confirming a metastasis or its recurrence, and selecting a Meanwhile, Torregrosa et al. performed 99m Tc-MIBI scintigraphy in patients with PHPT (n=16) and SHPT (n=22) and found 93% and 54% sensitivities for lesion localization in cases with PHPT and SHPT, respectively. They found that 99m Tc-MIBI planar scintigraphy can be used as the imaging technique of choice for preoperative localization of an abnormal parathyroid gland in patients with PHPT, but only as a complementary imaging technique in patients with SHPT (7).
In addition, Caldarella et al. reviewed 24 studies on 471 patients with SHPT, using 99m Tc-MIBI planar images. The sensitivity and specificity of 99m Tc-MIBI planar scintigraphy in detecting hyperplastic glands in SHPT patients were 58% and 93%, respectively. Considering the inadequate diagnostic accuracy of this technique, it should not be considered a first-line diagnostic imaging method for preoperative localization in patients with SHPT (8).
In the present study, the detection rate of hyperplastic parathyroid glands, using 99m Tc-MIBI planar or fusion imaging, was poor. The degree of 99m Tc-MIBI uptake in parathyroid gland is influenced by the content of mitochondria-rich oxyphil cells. It is thought that 99m Tc-MIBI easily accumulates in parathyroid adenomas, which contain many oxyphil cells (9,10).
In our study, the detection rate of hyperplastic gland, using 99m Tc-MIBI planar, SPECT, and fusion imaging was poor. Although 99m Tc-MIBI planar scintigraphy was not successful in the localization of hyperplastic glands, in patient No. 6, fusion images were effective in the localization of hyperplastic gland with a faint abnormal uptake of 99m Tc-MIBI in the right lower parathyroid (Figure 2).
No previous studies have evaluated the correlation between the diagnostic ability of fusion images and the size of parathyroid lesions or hyperplastic glands, based on pathological evaluations. In the current study, size of lesions in pathological evaluations was used for making comparisons. It showed that fusion images could detect parathyroid adenomas with the greatest axial diameter of > 0.6 cm, while planar 99m Tc-MIBI scintigraphy and SPECT imaging were unable to detect parathyroid adenomas with the largest axial diameter of 1.0-1.2 cm.
It can be concluded that SPECT/CT fusion imaging is a more useful tool for the localization of parathyroid lesions in hyperparathyroidism, especially parathyroid adenomas, in comparison with planar 99m Tc-MIBI parathyroid scintigraphy or SPECT imaging.

Conflicts of interest
None of the authors have a direct or indirect financial interest in the products under investigation or the subject matter discussed in the article.